Non-invasive radio-imaging analysis, in particular for examining small animals in vivo, and method for using same

ABSTRACT

A non-invasive analysis device including a plurality of sensors ( 110 ) combined with collimating structures ( 120 ) having a common source focus (O) and processing means ( 300 ) providing an AND-type combinational logic function of the output of the sensors ( 110 ) for sensing two coincidently transmitted beams that are at least slightly angularly correlated.

The present invention relates to the field of non-invasive devices foranalysis by radio-imaging.

Numerous analysis devices have already been proposed which useradioactive markers (Geiger counters coupled to a collimator, gammacameras, etc.).

By utilizing the inherent property of radioactive marking which makes itpossible to obtain quantitative information regarding the distributionof the tracer, radio-imaging techniques constitute an important toolboth in the clinical field and in the field of fundamental research.

At present, the devices which are used most widely in this field belongto computer-aided emission tomography.

Computer-aided tomography has been developed along two different lines:the SPECT (Single Photon Emission Computed Tomography), which uses radioisotopes emitting a single photon by decay, for example ^(99m)Tc, andthe PET (Positron Emission Tomography) system, which uses radio isotopesin which two gamma radiation events are emitted simultaneously duringthe annihilation, in the tissue, of the positron produced by the decayof, for example, ¹⁸F.

Most SPECT systems are based on the use of one or more gamma cameraswhich are rotated about the object to be analyzed. A typical gammacamera consists of a multi-channel collimator, a large-area scintillatorcrystal, a light guide for optical coupling between the crystal and aset of photomultiplier tubes, and analog electronics for analyzing theamplitude of the signal and the position encoding. The entire device iscontained within lead shielding in order to minimize the backgroundnoise produced by sources lying outside the field of view of the camera.The operating principle of a gamma camera is as follows: a photon,produced by a decay event in the by a center-of-gravity technique and torecord and/or send it to a display device.

Positron emission tomography (PET) is another method which makes itpossible to achieve in vivo and non-invasive regional measurement ofphysiological and metabolic parameters. Positron-emitter radioelementsare isotopes having a surplus of protons with respect to their number ofneutrons. When a positron is almost at rest, an encounter with anelectron gives rise to an annihilation reaction which produces thesimultaneous emission of two gamma photons departing in almost oppositedirections. PET systems thus comprise an array of detectors in a ringwhich can detect the coincidence of two photons, as being indicative ofthe emission of the positron. The site of the annihilation then liessomewhere in the volume defined between the two detectors in question.

U.S. Pat. No. 4,288,697 describes a collimator formed by a stack ofplates which are provided with perforations that correspond to ahomothetic progression and are produced by chemical machining.

IEEE Transactions On Nuclear Science, Vol 41, no. 4, describes aconventional PET structure without a focusing collimating structure.

EP-A-0 289 737 describes a conventional scanner having a focal point.

Radio-pharmaceutical imaging constitutes an important tool in thediagnosis, characterization and treatment of diseases and functionaldisorders. However, before new pharmacological agents are used in man,it is generally necessary to characterize them in animal models in orderto determine its biochemical, metabolic and physiological effects.

Of course, this characterization presupposes the availability ofhigh-resolution imaging techniques in order to evaluate, ex vivo or invivo, the spatial concentrations of the tracer which is injected.

At the present time, the spatial resolution of conventional tomographsis from 5 to 7 mm in the case of PET systems and from 8 to 12 mm in thecase of SPECT systems. These values prove to be insufficient forcarrying out studies in small animals, for example for rat studies oftumors, the typical size of which is of a few mm, or the distribution ofneuroreceptors. In actual fact, it is necessary for a tomographdedicated to the imaging of small animals to be able to provide spatialresolutions of at least ˜2 mm.

Since 1990, a number of approaches based on PET and SPECT systems havebeen pursued in an attempt to achieve the desired performance.

However, these attempts at improvement have not yet been satisfactory,except at the cost of detection efficiency. The limitations of currenttomographs in terms of resolution do not therefore allow in vivo studiesto be extended to models on small animals, for which experimentationcould be carried out more precisely.

The object of the present invention is to improve this situation.

This object is achieved according to the present invention by virtue ofan analysis device comprising a plurality of detectors which areassociated with collimating structures having a common source focus anddetector output processing means, characterized in that the processingmeans perform a combinatorial logic function of the “AND” type on theoutput of the detectors in order to detect two coincidentally emittedradiation events that are at least slightly angularly correlated.

According to another characteristic of the invention, a multi-channelcollimator is provided which is formed by a stack of plates havingperforations, the thickness of the plates is less than the diameter ofthe perforations in the internal entry face of the collimator and thethickness of the span between the perforations is greater than thethickness of the plates.

According to an advantageous characteristic of the invention, theperforations in the plates are produced by chemical machining.

detecting these radiation events using a device of the aforementionedtype.

Other characteristics, objects and advantages of the present inventionwill emerge when reading the following detailed description, and withreference to the appended drawings which are given by way ofnon-limiting example, and in which:

FIG. 1 represents a general schematic view of an analysis deviceaccording to the present invention,

FIG. 2 represents a view, partially in section, of the detection part ofthis device,

FIG. 3 schematically represents a stack of plates forming a collimator,

FIG. 4 reprsents a structure for supporting of the detectors,

FIG. 5 represents a partial diagram of the processing of an acquisitioncircuit according to a first variant of the invention,

FIG. 6 schematically represents one form of energy/time conversion ofthe detected signals, according to a second variant of the invention,

FIG. 7 represents a circuit diagram for this purpose,

FIG. 8 represents time diagrams of the signals of this circuit, and

FIG. 9 represents the general structure of an acquisition circuit.

The analysis device according to the present invention essentiallycomprises:

a set of detectors 100,

means 200 which are designed to support a body C to be analyzed and toallow a controlled relative displacement between it and the set ofdetectors 100, and

processing means 300.

The set of detectors 100 comprises a plurality of detectors 110 focusedon a common source focus O. The detectors 110 are carried by a supportstructure 150.

The detectors 110 preferably cover a solid angle at least equal to 2πsteradians around the focus O.

According to the non-limiting particular embodiment represented in theappended figures, fifteen detectors 110 are provided, arranged incorrespondence with fifteen adjacent faces of an icosahedron.

Each detector 110 preferably comprises:

a collimator 120,

a scintillator 130,

an optical guide 135, and

a photomultiplier 140.

A detector 110 of this type constitutes a counter of gamma and/or Xradiation.

The collimators 120 are used to select the direction of the photonswhich are detected. They are formed by collimating structures that focuswith large solid angle.

The focused collimation allows preferential detection of the radiationoriginating from a small region of space around the focal point O. Acollimating structure of this type may be formed by a spherical cap withsectors or a polyhedron consisting of plane parts pierced with conicalradial holes and constructed with a material having high photoelectricabsorption power.

The conical radial holes preferably have at least substantially the sameentry radii. They also preferably have at least substantially the sameexit radii, the same vertex and are juxtaposed in a regular array withaxial symmetry. The various channels are separated by partitions whosethickness is tailored to the energy of the radiation emitted by thesource, so as to make it possible to absorb a high proportion of thoseprotons whose trajectory is oblique with respect to the channel axis. Inthis way, only the photons emitted at the focal point will have asignificant probability of reaching the scintillators 130.

In the scope of the present invention, as schematized in FIG. 3, thecollimators 120 are preferably made by stacking perforated plates 122having homothetic perforations 124.

The plates 122 are advantageously made of tungsten.

The reason for choosing tungsten is, on the one hand, its highabsorption power: it has an absorption coefficient which is 30% to 40%greater than that of lead in the 10-500 keV range. Further, itsmechanical properties ensure that the system is rigid and that the shapeof the holes 124 is precise.

Moreover, within the scope of the invention, the homothetic perforations124 made in the tungsten plates 122 are preferably obtained by chemicalmachining.

After lengthy studies and experiments, this technique was found to besuperior to other known piercing techniques, such as laser piercing orwire spark erosion.

Machining by chemical etching consists in depositing a photosensitiveresin on all the parts which are to be preserved, by making use of amask representing the part to be produced. The part is then immersed ina bath which chemically etches the unprotected regions to form thedesired openings 124.

As schematized in FIG. 3, the holes 124 in each plate 122 are cylindersthat are parallel to one another and orthogonal to the faces of theplates 122. The result of this is that the solid angle, with respect tothe source focus O, subtended by the aperture of a hole 124, decreaseswhen moving away from the normal N to the plates 122 which passesthrough their homothetic center O.

The radius r of the holes 124 in the entry face 123, the thickness d ofthe plates 122 and the focal length f are determined so as to conservean acceptable solid angle subtended by the aperture of each hole 124with respect to O.

The thickness d of the plates 122 is preferably less than the diameterof the holes 124 in the internal entry face 123 of the collimator, forexample equal to half this diameter, and the thickness of the span(septum) between the holes 124, in this internal face 123, is greaterthan or equal to the thickness of the plates 122 (i.e., for example, adistance between the centers of the holes to equal to three times theradius of the holes 124 on the internal face 123).

If the detectors 110 are assembled on a polyhedral support 150 of theregular icosahedron type, each collimation module 120 takes the form ofa truncated triangular pyramid.

According to one non-limiting particular embodiment, each collimator 120is formed by stacking 48 tungsten plates 122 having a thickness of 0.2mm and an array of holes 124 defining a focal length f of the order of 7cm, the holes 124 having, in the internal face 123 of the collimator, aradius of the order of 0.2 mm and an interaxial distance of the order0.5 mm.

More precisely, each collimator 120 may be formed by stacking 24different pairs of pairwise identical plates 122. In an arrangement ofthis type, each plate, of thickness d, is formed by juxtaposing twoidentical screens of thickness d/2. In this way, it is easy to produceholes 124 of diameter equal to d, with a separation between centersequal to 3d/2.

Yet more precisely, according to a non-limiting very particularembodiment, the radius of the holes 124 is 0.205 mm in the first plate122 and 0.231 mm in the last plate 122, the distance between centers ofthe holes 124 is 0.614 mm in the first plate 122 and 0.693 mm in thelast plate 122, the length of the edges of the first plate 122 is 87.2mm and 98.3 mm for the last plate 122, and the distance to the focalpoint is 71.6 mm for the first plate 122 and 80.8 mm for the last plate122.

The scintillator 130 is preferably formed by a single crystal ofthallium-activated sodium iodide (NaI(Tl)).

In the case of an arrangement of the icosahedral type, the scintillatorcrystal has the form of a prism with triangular cross section in orderto cover the entire exit surface of the collimator.

The light guide 135 provides optical coupling between each scintillatorcrystal 130 and the associated photomultiplier tube 140.

The structure 150 which supports the detectors 110 has to position thefocal points of the collimators 120 with sufficient precision, typicallyof the order of 0.1 mm. There are a number of possible alternativeembodiments for a support structure 150 of this type.

One particular embodiment, comprising a framework consisting of supportbars 152 connected in sets of 5 by their ends and arranged along theedges of an icosahedron, is represented in FIG. 4. The plates 122 of thecollimators 120 can be fixed on these bars 152 using rods 154 engaged inthe corners of the plates 122.

However, as a variant, the structure 150 may support the light guides135 of the detectors, instead of the collimators 120.

The system 200 for supporting and displacing the analyzed object isdesigned to define three degrees of freedom in linear displacement forthe analyzed object C with respect to the sensors 110. Thesedisplacements can be brought about using three controlled and identifiedmotorized shafts, schematically represented at 210 in FIG. 1, which aremutually orthogonal and associated with control means 220 which displacethe motors interactively in order to position the object C and define ananalysis region and a displacement step in order to automatically carryout the scan needed for acquisition.

The mechanism 210 for displacing each shaft may be composed of thefollowing units for each motorized shaft:

a translation table which drives the movement of a carriage by ascrew/nut system, over a travel of, for example, 10 cm, and

a stepper motor which allows controlled increments of, for example, 10μm on each translation table.

The image resulting from an acquisition is constructed on the basis ofthe number of photons detected at each position of the displacementsystem 210. During the acquisition, it is therefore necessary to avoidany movement of the analyzed object C with respect to the displacementsystem 210, so as not to introduce artefacts in the image.

The system 200/210 consequently needs to be equipped with a system forspecific positioning of the analyzed object.

By way of non-limiting example, in the case of imaging the brain of arat, it is simply sufficient to immobilize the rat's head. Thepositioning system used in this case may correspond to those which areknown in stereotaxy equipment. In this case, the head is immobilized atthree points: at the entries of the auricular orifices, with two bars ofadjustable position, and behind the incisors, with a bar on which theupper jaw bears.

The processing means 300 are designed to detect two temporallycoincident radiation events produced on all of the detectors 110,without possibly taking into consideration coincidences produced in thesame detector or those produced in diametrically opposite detectors.

An event is thus detected with all the more probability that itoriginates from the focal point by virtue of the combination of physicalcollimation, given by the collimating structure, and electroniccollimation, given by the coincident detection of the photons producedby the decay.

When two photons of equal energy are to be detected, the processing andacquisition electronics 300 may be particularly simple, as representedin FIG. 5.

Each detection line associated with a detector 110 comprises anamplifier 310 and a discriminator module 312 which define a windowaround the photopeak. The outputs of the single-channel analyzers 312are used to generate the coincidence signal in a time/amplitudeconverter 314. Three signals are sent to an interface card 316: thecoincidence signal output by the converter 314 and the two outputs ofthe single-channel analyzers 312, in the latter case with the object ofconstructing a single-photon image for each detector 110. An acquisitionsignal, generated by logic combination in a gate 318 of the single-eventimages originating from the discriminators 312, is also applied to theinterface card 316.

The device which has been described above and is illustrated in FIG. 5nevertheless soon becomes bulky and impractical when the intention isfor coincident detection, and from more than two detectors 110, of tworadiation events of different energy.

In order to resolve this difficulty, a specific acquisition device isproposed in the scope of the invention, which makes it possible, foreach detected event, to extract the energy of the event and the time atwhich is occurs, in order to test its temporal coincidence with anotherevent.

A device of this type carries out, for example, energy/time conversionand encodes the events in a signal whose width is proportional to theirenergy. A system of this type also permits intrinsic encoding of thetime of arrival of each event, and therefore permits coincidence tests.

The operating principle of a system for detecting coincidences which isbased on an energy/time converter is as follows. Two events are detectedon the detectors i and j respectively. Each energy/time converterproduces a signal whose width T is proportional to the energy impartedto the detector. If the widths Ti and Tj correspond to the energiesinvolved, the events are considered to be coincident if the differencebetween the start of the signal, t_(di)−t_(dj), is less than the widthof the coincidence window τ fixed beforehand.

FIG. 7 represents an illustrative embodiment of a circuit 320 accordingto the invention, which can perform energy/time conversion of this type,and FIG. 8 represents time diagrams of the signals taken from variouspoints in the circuit.

The circuit in FIG. 7 comprises:

a capacitor 321 capable of integrating the signal output by aphotomultiplier 140,

an output signal detector 322 for the photomultiplier,

a delay cell 323 initiated by the aforementioned detector 322,

a current source 324 which is connected in parallel with the capacitor321 and is driven by the output of the delay cell 323,

a comparator 325, one input of which is grounded and the other input ofwhich is connected to the capacitor 321, the output of this comparator325 constituting the output of the energy/time conversion device, and

a switch 326 which is controlled by the comparator 325 and can dischargethe capacitor 321.

This circuit 320 operates as follows.

The scintillation light produced by the interaction of an X or a γphoton in the Nal(Tl) crystal 130 is manifested, on the anode of thephotomultiplier 140, as a signal having a very fast rise (in absolutevalue) followed by a virtually exponential fall, typically with a timeconstant of the order of 230 ns. Since the integral of this response isproportional to the energy imparted by the radiation to the crystal, theobject of the energy/time converter 320 is to recover this integral inorder to modulate the width of a square-wave signal. The integral of theanode signal is recovered on the capacitor 321 over a predefined time.This time is obtained on the basis of the delay applied to the signalextracted from the last dynode of the photomultiplier 140 (signaldetection 322 and delay cell 323 modules). At the end of the integrationtime, the current generator 324, which is connected in parallel with thecapacitor 321, is turned on in order to bring about a linear dischargeof this capacitor. At the same time as the current generator 324 isstarted, the output of the flip-flop 325 which gives the output signalof the converter 320 changes to a logic state “1”. Wherein the voltageof the capacitor 321 passes through zero, the flip-flop 325 returns toits low state, thus interrupting the high level of the output signal,the current generator 324 is stopped and the capacitor 321 is dischargedfully by operating the switch 326.

FIG. 9 illustrates an illustrative embodiment of an acquisition circuit330 according to the embodiment.

This circuit 330 is designed to encode energies which, for example,range from ˜10 keV (27 keV for ¹²³I and ¹²⁵I) to ˜300 keV (245 keV for¹¹¹In) at a maximum counting rate of ˜10⁴ hits per second per detector.

The system 330 is, for example, composed of:

a set of (for example 15) detectors (scintillator 130+photomultiplier140),

one energy/time converter 320 coupled to each detector 110,

two detectors 331, 332, respectively for leading and trailing edges ofthe signals output by the converters 320,

a clock 333 for the time base of the signals,

two timers 334, 335 driven by the clock 333,

two address counters 336, 337 driven by the edge detectors 331, 332, and

two memories 338, 339 for cyclically and temporarily storing informationthen transferring it on to the bus 341 of a computer 342.

At the output of each energy/time converter 320, a signal is found whosewidth is proportional to the energy imparted to the detector 110. Thiswidth may, for example, vary from ˜10 ns for 3 keV to ˜1 μs for 300 keV.This readily permits a counting rate of 10⁵ hits per second. The timesof the leading and trailing edges of the signal are calculated using thetimers 334, 335 and clock 333, and are stored in the independentmemories 338, 339. Once acquisition has been completed in a voxel, thedata in the memories 338, 339 are transferred to the bus 341 of the PCin order to be processed using specific software.

Of course, the data acquisition method according to the presentinvention, with a view to imaging, comprises the initial step ofinjecting the body C to be analyzed with a radioactive marker capable ofemitting two coincident radiation events that are at least slightlyangularly correlated.

There are a number of possible variants for a marker of this type.

Attention may be drawn to at least three mechanisms of radioactivede-excitation which give rise to the emission of two coincident photonsthat are only slightly angularly correlated.

In the first of the de-excitation mechanisms (isobaric de-excitation ofthe nucleus), the decay of a parent nucleus produces an excited nucleuswhich changes to its ground state through a cascade, thus producing twocoincident gammas. An example of a radioelement which de-excites by thismechanism is ¹¹¹In. After an electron capture, ¹¹¹In (half-life: 2.8days), changes essentially to the 417 keV excited level of ¹¹¹Cd. Theground state of ¹¹¹Cd is reached by the cascade emission of one gamma of171 keV followed by another with 245 keV; the half-life of the 245 keVlevel is 85 ns.

The other two mechanisms relate to radioelements whose decay starts withelectron capture, and this serves to provide the first photon of thecoincident pair. Specifically, in electron capture, the X_(k) emissionresulting from the rearrangement of the inner electron shells isutilized to provide a first photon. The deexcitation of the daughternucleus gives rise to the second photon, and there are two possible waysthat this may take place. If the de-excitation is radiative, there willbe a γ photon coincidence with the X_(k) photon. If the de-excitationtakes place through internal conversion, there will also be electronrearrangement and emission of an X_(k) photon in coincidence with thatof the electron capture. Two isotopes of iodine (Z=53) give an exampleof these two coincidence mechanisms: ¹²³I (half-life: 13 h) and ¹²⁵I(half-life: 60 days). In both cases, the emitted X_(k) radiation has anenergy of about 27 keV, the probability of capturing an electron in theK shell is 80% and the fluorescence efficiency is 86%. In the case of¹²³I, the electron capture leads to an excited state of ¹²³Te, whichchanges to the ground state by emitting a 159 keV gamma, the X_(k)-γcoincidence factor is about 70%. In the case of ¹²⁵I, the excited stateof the daughter nucleus at an energy of 35 keV, and the change to theground state takes place either by emission of a gamma (7% probability)or by internal conversion; the coincidence factor for X_(k)-γ plusX_(k)-X_(k) is 60%.

The invention is not limited to the use of the aforementionedradioelements: ¹²³I, ¹²⁵I and ¹¹¹In, but extends to any other equivalentradioelement which can emit at least two temporarily coincidentradiation events, for example γ-γ, γ-X or X-X, that are at leastslightly angularly correlated.

After or before the radio tracer is injected, the body C to be analyzedis placed in the collimating detection structure 100.

The radiation events which are emitted by the object C and pass throughthe collimators 120 are detected by all the detectors 110 (scintillators130+photomultipliers 140). The signal which is output by the detectors110 and has been amplified and processed in the means 310, 320, 330 issent to a computer 342 whose task is to acquire and store it. Theprocessing electronics 310, 320, 330 deliver either the signalsindicating coincidence between any two detectors 110, or a set ofsignals so that the coincidences which occur can be recovered aposteriori.

The coincidence detection makes it possible to optimize the spatialresolution and to reject signals originating from points lying outsidethe focal point.

Displacing the focal point of the collimators 120 by scanning throughthe volume of the region of interest during the acquisition makes itpossible to construct the image of the object C voxel by voxel. It isthus unnecessary to use an algorithm for reconstructing the image, whichmay in particular amplify the statistical fluctuations on thereconstructed image, as in the case of the SPECT and PET techniques, andthe image may, according to the invention, be displayed voxel by voxelas the acquisition proceeds.

The present invention may give rise to a number of applications whichrequire measurement of the concentration of radioactively markedchemical species, non-limiting examples which may be mentioned of whichapplications include the in vivo examination of small animals, inparticular within the scope of clinical research, relating for exampleto the detection of cardiovascular lesions, oncology, the detection andmonitoring of tumors, studying the distribution of neuroreceptors,displaying the functions of the brain (in the case of neurodegenerativediseases, such as Parkinson's or Alzheimer's diseases, or Huntington'sdisease; or in the event of psychiatric disorders, such as inschizophrenia), gene therapy or, more generally, neurobiology orneuropharmacology in order to evaluate the effectiveness of treatmentsbased on the administration of neuroprotective agents and on neuralgrafting.

The present invention is not, of course, limited to the particulararrangements which have just been described, but extends to any variantin accordance with its spirit.

The use of the device and the implementation of the method which weredescribed above can be carried out by any authorized individual withoutrequiring particular knowledge in the medical field.

What is claimed is:
 1. Device for non-invasive analysis by radio-imagingof a body receiving a marker which can generate two coincidentallyemitted radiation events that are not angularly correlated, comprising aplurality of detectors supported in non-coplanar directions for coveringa spatial field around the body, the detectors being associated withrespective collimating structures having a common source focus anddetector output processing means wherein the processing means comprisemeans sensitive to the output of each one of the plurality of detectorsand are able to check detection of emitted radiation events on anywhatever two detectors of the plurality of detectors, in a specificdeadline, so as to perform a combinatorial logic function of the “AND”type on the output of the detectors in order to detect twocoincidentally emitted radiation events that are not angularlycorrelated generated by the marker.
 2. Device according to claim 1,characterized in that it comprises means for counting radioactiveradiation events.
 3. Device according to claim 1, characterized in thatit further comprises means which are designed to support the body to beanalyzed, and to allow a controlled relative displacement between thebody and the plurality of detectors.
 4. Device according to claim 1,characterized in that the plurality of detectors cover a spatial fieldat least equal to 2π steradians around the focus.
 5. Device according toclaim 1, characterized in that the plurality of detectors are arrangedin accordance with the faces of an icosahedron.
 6. Device according toclaim 1, wherein the plurality of detectors comprises fifteen detectors.7. Device according to claim 1, characterized in that each of theplurality of detectors comprises a collimator, a scintillator, anoptical guide and a photomultiplier.
 8. Device according to claim 1,characterized in that each collimating structure comprises conicalradial holes.
 9. Device according to claim 1, further comprising astructure which is intended to support the plurality of detectors and isin the form of a framework consisting of bars connected by their ends.10. Device according to claim 1, characterized in that it comprisesmeans which can effect a relative displacement which is controlled andidentified on the basis of three orthogonal axes between the body to beanalyzed and the plurality of detectors.
 11. Device according to claim1, comprising processing means comprising energy/time conversion meanswhich can encode the detected events in the form of signals whose widthis proportional to the energy of the event.
 12. Device according toclaim 11, characterized in that the processing means comprise: acapacitor capable of integrating the signal output by a photomultiplier,an output signal detector for the photomultiplier, a delay cellinitiated by the aforementioned detector, a current source which isconnected in parallel with the capacitor and is driven by the output ofthe delay cell, a comparator, one input of which is grounded and theother input of which is connected to the capacitor, the output of thiscomparator constituting the output of the energy/time conversion means,and a switch which is controlled by the comparator and can discharge thecapacitor.
 13. Device according to claim 11, characterized in that theprocessing means comprises timers which are driven by a clock and aredesigned to define the trip times of the signal output by theenergy/time conversion means.
 14. Device according to claim 13,characterized in that the timers are controlled by detectors of leadingand trailing edges of the signals output by the energy/time conversionmeans.
 15. Device non-invasive analysis by radio-imaging of a bodyreceiving a marker which can generate two coincidentally emittedradiation events that are not angularly correlated, comprising aplurality of detectors supported in non-coplanar directions for coveringa spatial field at least equal to 2π steradians around the body, saiddetectors being associated with respective collimating structures havinga common source focus and detector output processing means wherein theprocessing means comprises means sensitive to the output of each one ofsaid plurality of detectors and are able to check detection of emittedradiation events on any whatever couple of two detectors belonging tosaid plurality of detectors, in a specific deadline, so as to perform acombinatorial logic function of the “AND” type on the output of thedetectors in order to detect two coincidentally emitted radiation eventsthat are not angularly correlated generated by said marker.
 16. Devicefor non-invasive analysis of radio-imaging of a body receiving a markerwhich can generate two coincidentally emitted radiation events that arenot angularly correlated, comprising a plurality of detectors supportedin accordance with the faces of an icosahedron in non-coplanardirections for covering a spatial field at least equal to 2π steradiansaround the body, said detectors each comprising a collimator, ascintillator, an optical guide and a photomultiplier, said collimatorshaving a common source focus and detector output processing means,wherein the device further comprises means which are designed to supportthe body to be analyzed and to allow a controlled relative displacementbetween the body and the plurality of detectors and wherein theprocessing means comprises means sensitive to the output of each one ofsaid plurality of detectors and are able to check detection of emittedradiation events on any whatever couple of two detectors belonging tosaid plurality of detectors, in a specific deadline, so as to perform acombinatorial logic function of the “AND” type on the output of thedetectors in order to detect two coincidentally emitted radiation eventsthat are not angularly correlated generated by said marker.
 17. Methodfor non-invasive analysis by radio-imaging, characterized in that itcomprises the steps consisting in: injecting, into a body to beanalyzed, a marker which can generate two coincidentally emittedradiation events that are not angularly correlated, and detecting theseradiation events using an analysis device comprising a plurality ofdetectors which are associated with collimating structures having acommon source focus and processing means performing a combinatoriallogic function of the “AND” type on the output of the detectors in orderto detect two coincidentally emitted radiation events that are notangularly correlated.
 18. Method according to claim 17, characterized inthat the marker which is used is designed to emit two coincidentallyemitted radiation events that are at least slightly angularly correlatedthrough atomic (X emitted following electron capture or internalconversion) or nuclear origin (gamma emitted during the isobaricde-excitation of a nucleus).
 19. Method according to claim 17,characterized in that the marker which is used is chosen from the groupcomprising ¹²³I, ¹²⁵I, ¹¹¹In.
 20. Method according to claim 17,characterized in that the image of the body to be analyzed isconstructed voxel by voxel.